a surgical anesthesia; for example, fentanyl and midazolam may be used in concert or ketamine and medetomidine may be combined (Hedenqvist and Hellebrekers, 2003). Using local anesthetics in combination with a general anesthetic is another example of a balanced anesthesia regimen, the benefit being that local anesthetics can reduce the need for general anesthesia and side effects associated with higher doses of general anesthesia (Gordon et al., 2002).

Analgesia is the inability to feel pain; an analgesic drug relieves pain but does not cause a loss of awareness. Analgesics include opioid drugs, such as morphine, and NSAIDs, such as aspirin and ibuprofen (NRC, 1992). There is evidence that surgery (or tissue injury) induces sensitization of central neural function, causing nociceptive inputs from the surgical wound to be perceived as more painful (hyperalgesia) than they would otherwise have been, and causes innocuous inputs to give rise to pain (allodynia). Studies have shown that preemptive analgesia (such as opiates, local anesthetics, or NSAIDs) prevents this sensitizing, reducing postoperative pain intensity and decreasing postoperative analgesic requirements for periods much longer than the duration of action of the preemptively administered analgesic (Coderre et al., 1993). Researchers should be encouraged to preemptively use analgesics.

Sedatives and anxiolytics may be used for the relief of non-pain-induced distress. They are often combined with analgesics to produce a state free of pain and distress—for example, in the management of postsurgical pain or pain associated with disease—and are also useful for restraint during minor procedures (NIH, 1991; NRC, 1992).

Systemic paralysis is commonly used in neuroscience experiments. These experiments require that the animal be paralyzed with a neuromuscular blocking agent to prevent movement, such as movement of the ocular muscles during visual experiments. Neuromuscular blocking agents are used only in fully anesthetized animals (NRC, 1996). They do not interact substantially with anesthetics and analgesics, but they leave an animal unable to respond behaviorally to pain or distress. That can make it difficult to evaluate the depth of anesthesia and the adequacy of analgesia, so other signs of pain or distress must be used, such as lacrimation, salivation, reactivity of heart rate and arterial blood pressure to noxious stimuli, or electroencephalographic recordings (NIH, 1991). Such signs are not adequate singly, but in combination they can provide valuable information about an animal’s physiologic status (NIH, 1991). In addition, care should be taken to ensure that the animal has recovered control of respiration and locomotion before it is returned to the home cage. A detailed discussion of monitoring paralyzed animals can be found in Chapter 5.

It is important to confer with a laboratory-animal veterinarian to develop an adequate anesthetic and analgesic regimen. In fact, the AWRs states that a veterinarian be consulted during the planning of any procedure that could cause pain in animals (AWR 2.31(d)(1)(iv)(B)). Many resources are available to help the investigator and laboratory-animal veterinarian to develop a balanced anesthetic



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